19-44708123-C-T

Variant names:

• chr19-44708123-C-T
• rs61744494
• NM_001039213.4:c.1203C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001039213.4(CEACAM16):​c.1203C>T​(p.Tyr401Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000516 in 1,609,188 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0025 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00030 (4 hom.)
• Consequence: CEACAM16 NM_001039213.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.53
• Publications: 0 publications found

Genes affected

CEACAM16 (HGNC:31948): (CEA cell adhesion molecule 16, tectorial membrane component) The protein encoded by this gene is a secreted glycoprotein that in mouse interacts with tectorial membrane proteins in the inner ear. The encoded adhesion protein is found in cochlear outer hair cells and appears to be important for proper hearing over an extended frequency range. Defects in this gene likely are a cause of non-syndromic autosomal dominant hearing loss. [provided by RefSeq, May 2012]

CEACAM16-AS1 (HGNC:55317): (CEACAM16, CEACAM19 and PVR antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 19-44708123-C-T is Benign according to our data. Variant chr19-44708123-C-T is described in ClinVar as Benign. ClinVar VariationId is 504819.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.53 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00255 (388/152338) while in subpopulation AFR AF = 0.00892 (371/41576). AF 95% confidence interval is 0.00817. There are 0 homozygotes in GnomAd4. There are 184 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 4 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039213.4. 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
	CEACAM16	NM_001039213.4	MANE Select	c.1203C>T	p.Tyr401Tyr	synonymous	Exon 6 of 7	NP_001034302.2
	CEACAM16-AS1	NR_186815.1		n.348-8946G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEACAM16	ENST00000587331.7	TSL:1 MANE Select	c.1203C>T	p.Tyr401Tyr	synonymous	Exon 6 of 7	ENSP00000466561.1
	CEACAM16	ENST00000405314.2	TSL:5	c.1203C>T	p.Tyr401Tyr	synonymous	Exon 5 of 6	ENSP00000385576.1
	CEACAM16-AS1	ENST00000590796.1	TSL:5	n.314+7827G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00256 AC: 389 AN: 152220 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00897

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000916

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000514 AC: 122 AN: 237446 AF XY: 0.000341

Gnomad AFR exome AF: 0.00763

Gnomad AMR exome AF: 0.000298

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000187

Gnomad OTH exome AF: 0.000342

GnomAD4 exome AF: 0.000304 AC: 443 AN: 1456850 Hom.: 4 Cov.: 30 AF XY: 0.000283 AC XY: 205 AN XY: 724184

African (AFR) AF: 0.0105 AC: 352 AN: 33374

American (AMR) AF: 0.000476 AC: 21 AN: 44148

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25962

East Asian (EAS) AF: 0.00 AC: 0 AN: 39490

South Asian (SAS) AF: 0.0000235 AC: 2 AN: 85100

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52922

Middle Eastern (MID) AF: 0.00122 AC: 7 AN: 5750

European-Non Finnish (NFE) AF: 0.0000144 AC: 16 AN: 1109884

Other (OTH) AF: 0.000747 AC: 45 AN: 60220

GnomAD4 genome AF: 0.00255 AC: 388 AN: 152338 Hom.: 0 Cov.: 32 AF XY: 0.00247 AC XY: 184 AN XY: 74500

African (AFR) AF: 0.00892 AC: 371 AN: 41576

American (AMR) AF: 0.000915 AC: 14 AN: 15298

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68038

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.000741 Hom.: 0

Bravo AF: 0.00294

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	6.0
DANN	Benign	0.53
PhyloP100		1.5
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs61744494; hg19: chr19-45211395;