rs73419912

Variant names:

• chr7-107791855-G-A
• rs73419912
• NM_000111.3:c.357C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-107791855-G-A
• chr7-107791855-G-T
• chr7-107791855-G-C

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_000111.3(SLC26A3):​c.357C>T​(p.Phe119Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00175 in 1,612,592 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0044 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (5 hom.)
• Consequence: SLC26A3 NM_000111.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.455
• Publications: 7 publications found

Genes affected

SLC26A3 (HGNC:3018): (solute carrier family 26 member 3) The protein encoded by this gene is a transmembrane glycoprotein that transports chloride ions across the cell membrane in exchange for bicarbonate ions. It is localized to the mucosa of the lower intestinal tract, particularly to the apical membrane of columnar epithelium and some goblet cells. The protein is essential for intestinal chloride absorption, and mutations in this gene have been associated with congenital chloride diarrhea. [provided by RefSeq, Oct 2008]

SLC26A3 Gene-Disease associations (from GenCC):

• congenital secretory chloride diarrhea 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 7-107791855-G-A is Benign according to our data. Variant chr7-107791855-G-A is described in ClinVar as Benign. ClinVar VariationId is 776252.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00437 (665/152188) while in subpopulation AFR AF = 0.0133 (553/41536). AF 95% confidence interval is 0.0124. There are 4 homozygotes in GnomAd4. There are 306 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000111.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC26A3	NM_000111.3	MANE Select	c.357C>T	p.Phe119Phe	synonymous	Exon 4 of 21	NP_000102.1	P40879

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC26A3	ENST00000340010.10	TSL:1 MANE Select	c.357C>T	p.Phe119Phe	synonymous	Exon 4 of 21	ENSP00000345873.5	P40879
	SLC26A3	ENST00000852261.1		c.357C>T	p.Phe119Phe	synonymous	Exon 4 of 21	ENSP00000522320.1
	SLC26A3	ENST00000852262.1		c.357C>T	p.Phe119Phe	synonymous	Exon 4 of 21	ENSP00000522321.1

Frequencies

GnomAD3 genomes AF: 0.00437 AC: 665 AN: 152070 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0134

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00104

Gnomad OTH AF: 0.00240

GnomAD2 exomes AF: 0.00171 AC: 431 AN: 251348 AF XY: 0.00148

Gnomad AFR exome AF: 0.0140

Gnomad AMR exome AF: 0.00119

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000880

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00148 AC: 2157 AN: 1460404 Hom.: 5 Cov.: 29 AF XY: 0.00138 AC XY: 1005 AN XY: 726596

African (AFR) AF: 0.0157 AC: 525 AN: 33438

American (AMR) AF: 0.00112 AC: 50 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.000151 AC: 6 AN: 39668

South Asian (SAS) AF: 0.00143 AC: 123 AN: 86234

European-Finnish (FIN) AF: 0.000112 AC: 6 AN: 53398

Middle Eastern (MID) AF: 0.000694 AC: 4 AN: 5762

European-Non Finnish (NFE) AF: 0.00121 AC: 1344 AN: 1110720

Other (OTH) AF: 0.00164 AC: 99 AN: 60338

GnomAD4 genome AF: 0.00437 AC: 665 AN: 152188 Hom.: 4 Cov.: 32 AF XY: 0.00411 AC XY: 306 AN XY: 74410

African (AFR) AF: 0.0133 AC: 553 AN: 41536

American (AMR) AF: 0.00170 AC: 26 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5172

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4822

European-Finnish (FIN) AF: 0.0000944 AC: 1 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00104 AC: 71 AN: 68004

Other (OTH) AF: 0.00237 AC: 5 AN: 2106

Alfa AF: 0.0106 Hom.: 28

Bravo AF: 0.00488

EpiCase AF: 0.000818

EpiControl AF: 0.00124

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Congenital secretory diarrhea, chloride type (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	2.8
DANN	Benign	0.55
PhyloP100		-0.46
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.35		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.35		Position offset: -25

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs73419912; hg19: chr7-107432300; COSMIC: COSV104641910; COSMIC: COSV104641910;