7-107661378-C-T

Variant names:

• chr7-107661378-C-T
• rs55753070
• NM_000441.2:c.-3-261C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000441.2(SLC26A4):​c.-3-261C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0246 in 579,984 control chromosomes in the GnomAD database, including 277 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (46 hom., cov: 32)
  • Exomes 𝑓: 0.027 (231 hom.)
• Consequence: SLC26A4 NM_000441.2 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.423
• Publications: 1 publications found

Genes affected

SLC26A4 (HGNC:8818): (solute carrier family 26 member 4) Mutations in this gene are associated with Pendred syndrome, the most common form of syndromic deafness, an autosomal-recessive disease. It is highly homologous to the SLC26A3 gene; they have similar genomic structures and this gene is located 3' of the SLC26A3 gene. The encoded protein has homology to sulfate transporters. [provided by RefSeq, Jul 2008]

SLC26A4-AS1 (HGNC:22385): (SLC26A4 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 7-107661378-C-T is Benign according to our data. Variant chr7-107661378-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1217919.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0187 (2854/152350) while in subpopulation NFE AF = 0.027 (1839/68018). AF 95% confidence interval is 0.026. There are 46 homozygotes in GnomAd4. There are 1328 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 46 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC26A4	NM_000441.2	c.-3-261C>T		intron_variant	Intron 1 of 20	ENST00000644269.2	NP_000432.1
SLC26A4-AS1	NR_028137.1	n.197+224G>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC26A4	ENST00000644269.2	c.-3-261C>T		intron_variant	Intron 1 of 20		NM_000441.2	ENSP00000494017.1

Frequencies

GnomAD3 genomes AF: 0.0188 AC: 2856 AN: 152232 Hom.: 46 Cov.: 32

Gnomad AFR AF: 0.00463

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0143

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.0261

Gnomad FIN AF: 0.00649

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0270

Gnomad OTH AF: 0.0234

GnomAD4 exome AF: 0.0266 AC: 11388 AN: 427634 Hom.: 231 Cov.: 2 AF XY: 0.0278 AC XY: 6263 AN XY: 225504

African (AFR) AF: 0.00461 AC: 54 AN: 11702

American (AMR) AF: 0.0159 AC: 287 AN: 18014

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 1452 AN: 13034

East Asian (EAS) AF: 0.00 AC: 0 AN: 29282

South Asian (SAS) AF: 0.0333 AC: 1511 AN: 45442

European-Finnish (FIN) AF: 0.00997 AC: 277 AN: 27784

Middle Eastern (MID) AF: 0.0417 AC: 78 AN: 1870

European-Non Finnish (NFE) AF: 0.0275 AC: 7022 AN: 255744

Other (OTH) AF: 0.0286 AC: 707 AN: 24762

GnomAD4 genome AF: 0.0187 AC: 2854 AN: 152350 Hom.: 46 Cov.: 32 AF XY: 0.0178 AC XY: 1328 AN XY: 74496

African (AFR) AF: 0.00462 AC: 192 AN: 41598

American (AMR) AF: 0.0143 AC: 219 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 351 AN: 3470

East Asian (EAS) AF: 0.000773 AC: 4 AN: 5172

South Asian (SAS) AF: 0.0255 AC: 123 AN: 4828

European-Finnish (FIN) AF: 0.00649 AC: 69 AN: 10630

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0270 AC: 1839 AN: 68018

Other (OTH) AF: 0.0232 AC: 49 AN: 2116

Alfa AF: 0.0231 Hom.: 9

Bravo AF: 0.0194

Asia WGS AF: 0.0100 AC: 35 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 24, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	6.8
DANN	Benign	0.82
PhyloP100		0.42
PromoterAI		0.026	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs55753070; hg19: chr7-107301823;