19-44703407-C-T

Variant names:

• chr19-44703407-C-T
• rs191552868
• NM_001039213.4:c.96C>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.96C>T​(p.Ser32Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00162 in 1,613,780 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0018 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (6 hom.)
• Consequence: CEACAM16 NM_001039213.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.223
• 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=-0.73).
• BP6: Variant 19-44703407-C-T is Benign according to our data. Variant chr19-44703407-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 226512.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.223 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00183 (279/152306) while in subpopulation AMR AF = 0.00961 (147/15296). AF 95% confidence interval is 0.00834. There are 2 homozygotes in GnomAd4. There are 133 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 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.96C>T	p.Ser32Ser	synonymous	Exon 3 of 7	NP_001034302.2	Q2WEN9
	CEACAM16-AS1	NR_186815.1		n.348-4230G>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.96C>T	p.Ser32Ser	synonymous	Exon 3 of 7	ENSP00000466561.1	Q2WEN9
	CEACAM16	ENST00000405314.2	TSL:5	c.96C>T	p.Ser32Ser	synonymous	Exon 2 of 6	ENSP00000385576.1	Q2WEN9
	CEACAM16-AS1	ENST00000590796.1	TSL:5	n.315-4230G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00184 AC: 280 AN: 152188 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00975

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00144

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00198 AC: 491 AN: 248354 AF XY: 0.00168

Gnomad AFR exome AF: 0.000195

Gnomad AMR exome AF: 0.00788

Gnomad ASJ exome AF: 0.000299

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000836

Gnomad NFE exome AF: 0.00165

Gnomad OTH exome AF: 0.00133

GnomAD4 exome AF: 0.00160 AC: 2332 AN: 1461474 Hom.: 6 Cov.: 32 AF XY: 0.00154 AC XY: 1117 AN XY: 727048

African (AFR) AF: 0.000239 AC: 8 AN: 33480

American (AMR) AF: 0.00901 AC: 403 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.000191 AC: 5 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.000921 AC: 49 AN: 53200

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5758

European-Non Finnish (NFE) AF: 0.00158 AC: 1757 AN: 1111862

Other (OTH) AF: 0.00179 AC: 108 AN: 60370

GnomAD4 genome AF: 0.00183 AC: 279 AN: 152306 Hom.: 2 Cov.: 32 AF XY: 0.00179 AC XY: 133 AN XY: 74470

African (AFR) AF: 0.000385 AC: 16 AN: 41570

American (AMR) AF: 0.00961 AC: 147 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.000942 AC: 10 AN: 10614

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

European-Non Finnish (NFE) AF: 0.00144 AC: 98 AN: 68024

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.00136 Hom.: 0

Bravo AF: 0.00266

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00120

EpiControl AF: 0.00172

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	2.7
DANN	Benign	0.59
PhyloP100		-0.22
Mutation Taster		=100/0	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: rs191552868; hg19: chr19-45206677;